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Different types of synaptic triads in the monkey dorsal lateral geniculate nucleus.

Characteristic synaptic complexes, the triadic synapses, were investigated in long series of sections of parvicellular and magnocellular laminae of the monkey lateral geniculate nucleus. Electron microscopic observations revealed the presence of different triadic types, the intercalated element being in all cases a presynaptic dendrite or soma of an interneuron (I-cell), and the output component being constantly a dendrite or soma of a geniculocortical projection or principal neuron (P-cell). The axonal input to the triads, however, was found to be of three different types: (1) the majority were retinal axon terminals; (2) a smaller fraction were the axonal endings of corticogeniculate fibers, always connected to thin, distal P-cell dendrites; (3) others were terminals with pleomorphic or flattened, small synaptic vesicles, probably belonging to axons of I-cells and/or of thalamic reticular nucleus origin. It was observed also that the retinal terminals established multiple synaptic contacts with both P-cell and I-cell dendrites. Essentially, two types of triadic arrangements with retinal input were recognized: the "simple" unit, frequent in parvicellular laminae, in which the retinal axon was accompanied by only 1-2 presynaptic dendrites; and the "complex" unit, found mostly in the magnocellular laminae, characterized by the presence of up to eight presynaptic dendrites. In the glomerular "complex" units, "closely packed" classical triads, with the three synaptic junctions localized close to each other, coexisted with triads "at a distance" where the synapses were distributed relatively far from each other. The coupling by presynaptic dendrites of "closely-packed" and "at a distance" triads resulted in the formation of multiple triadic arrangements. Since cortical and inhibitory triads were never seen to be involved in multiple triadic complexes, the latter appeared exclusively retinal in nature. The possible functional significance of multiple triads in "ON-gating" operation is briefly discussed.

Animals↗

Phosphorylation of the 1,4-dihydropyridine receptor of the voltage-dependent Ca2+ channel by an intrinsic protein kinase in isolated triads from rabbit skeletal muscle.

Isolated triads from rabbit skeletal muscle were shown to contain an intrinsic protein kinase which was neither Ca2+/calmodulin-dependent nor cAMP-dependent. The protein substrates phosphorylated by this protein kinase exhibited apparent molecular weights of 300,000, 170,000, 90,000, 80,000, 65,000, 56,000, 52,000, 51,000, 40,000, 25,000, 22,000, and 15,000. Purification of the 1,4-dihydropyridine receptor from phosphorylated triads has demonstrated that the 170,000- and 52,000-Da subunits of the 1,4-dihydropyridine receptor are phosphorylated by this intrinsic protein kinase in isolated triads. Monoclonal antibodies to the 170,000-Da subunit of the dihydropyridine receptor immunoprecipitated the 170,000-Da phosphoprotein from detergent extracts of phosphorylated triads. The mobility of the 170,000-Da phosphoprotein in sodium dodecyl sulfate-polyacrylamide gels was not changed with or without reduction, demonstrating that the 170,000-Da phosphoprotein is not the glycoprotein subunit of the receptor. Our results demonstrate that the 170,000- and 52,000-Da subunits of the dihydropyridine receptor are phosphorylated by an intrinsic protein kinase in isolated triads. In addition, our results also demonstrate that the 175,000-Da glycoprotein subunit of the dihydropyridine receptor is not phosphorylated in isolated triads by the intrinsic protein kinase, cAMP-dependent protein kinase, or endogenous Ca2+/calmodulin-dependent protein kinase.

Animals↗

[Analysis of the structure of the depressive triad as a diagnostic and prognostic indicator].

In order to ascertain the diagnostic and prognostic importance of the structure of the depressive triad, the authors conducted a clinical psychopathologic study of 173 patients (88 males and 85 females) with depressions (manic-depressive psychosis, schizophrenia, residual-organic and vascular cerebral impairments, psychogenic depression). An analysis of the structure of the depressive triad was made based on the concept of heterogeneity of the depressive affect, with such acknowledged major components as melancholy, anxiety, and apathy. Depending on the nature of the leading elementary affect, three types of the depressive triad were identified, namely, melancholy, anxiety and apathy depressive triads. According to the criterion of qualitative and quantitative correlation between the triad components (ideational and motor) and the leading affect, harmonic, disharmonic and dissociated variants were identified within every type. The regular features of the time-course of the triad were established: from the initial stages to the over picture and then to the reduction of depression. These regularities were characterized by definite nosological preference, and may be helpful in the differential diagnosis and also be used as predictors of a protracted course of depression.

Adolescent↗

pH-sensitive calcium release in triads from frog skeletal muscle. Rapid filtration studies.

Triad vesicles from frog skeletal muscle exhibited calcium-induced calcium release highly sensitive to extravesicular pH; calcium induced release at pH > 7.4 but not at pH 6.8. In contrast, triads isolated from rabbit skeletal muscle exhibited significant calcium-induced calcium release at pH 6.8. At pH 7.4, there was no stimulation of calcium release in triads from frog at pCa 7, maximum stimulation at pCa 5, and complete inhibition at pCa 3. Addition of ATP at pCa 5, pH 6.8, induced calcium release with the same high rate constants in both preparations. In triads from frog, ATP-induced calcium release at pCa 5 had the same kinetics at pH 6.8 and 7.4, whereas ATP-induced calcium release at pCa > 8, pH 6.8, was partial, with a decrease in the amounts released but not in rate constants. In contrast, triads from rabbit displayed the opposite behavior, with a decrease in rate constants but not in the amounts of calcium released at pCa > 8, pH 6.8. In triads from frog ATP-induced calcium release decreased at pCa < 4, to reach total inhibition at pCa 2; addition of magnesium (free > 0.5 mM) completely abolished ATP-induced calcium release at pH 6.8, pCa 7 or 5. The potential physiological relevance of these results is discussed.

Adenosine Triphosphate↗

Scanning tunneling microscopy and spectroscopy of donor-acceptor-donor triads at the liquid/solid interface.

By means of scanning tunneling microscopy (STM), the self-assembly of two organic donor-acceptor-donor triads (donor=oligo(p-phenylene vinylene) (OPV); acceptor=perylene diimide (PDI)) and their mixtures has been investigated at the liquid/solid interface. Both triads differ in the nature of the substituents and, therefore, in the redox properties of the central perylene diimide unit (H or Cl). Thanks to the submolecular resolution, the distinct electronic properties of the units, within a triad and between the two triads, are reflected by the relative STM contrast in the bias-dependent imaging experiments. Moreover, scanning tunneling spectroscopy reveals an inverse rectifying behavior of the OPV and H-substituted PDI units, which is discussed in the framework of quasi-resonant tunneling. A striking difference is observed for the Cl-substituted triad.

Journal Article↗

A two-stranded template-based approach to G.(C-A) triad formation: designing novel structural elements into an existing DNA framework.

We have designed a DNA sequence, d(G-G-G-T-T-C-A-G-G), which dimerizes to form a 2-fold symmetric G-quadruplex in which G(syn). G(anti).G(syn).G(anti) tetrads are sandwiched between all trans G. (C-A) triads. The NMR-based solution structural analysis was greatly aided by monitoring hydrogen bond alignments across N-H...N and N-H...O==C hydrogen bonds within the triad and tetrad, in a uniformly ((13)C,(15)N)-labeled sample of the d(G-G-G-T-T-C-A-G-G) sequence. The solution structure establishes that the guanine base-pairs with the cytosine through Watson-Crick G.C pair formation and with adenine through sheared G.A mismatch formation within the G.(C-A) triad. A model of triad DNA was constructed that contains the experimentally determined G.(C-A) triad alignment as the repeating stacked unit.

Base Pair Mismatch↗

Effects of fluvastatin slow-release (XL 80 mg) versus simvastatin (20 mg) on the lipid triad in patients with type 2 diabetes.

The lipid triad is the association of small, dense (sd) low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and hypertriglyceridemia, all of which play a role in coronary artery disease in patients with type 2 diabetes. Although statins have demonstrated clear positive effects on cardiovascular morbidity/mortality in patients with diabetes and on single components of the lipid triad, it remains controversial whether they affect all components of the triad in these patients. Therefore, we performed a single-center, parallel-group, prospective, randomized, open-label, blinded-endpoint (PROBE)-type comparison of fluvastatin extended-release (XL) 80 mg (n=48) and simvastatin 20 mg (n=46), each given once daily for 2 months to patients with type 2 diabetes with the lipid triad, who were enrolled after a 1-month lifestyle modification and dietary intervention program. After fluvastatin therapy, LDL (-51%; P<.01), apolipoprotein B (ApoB; -33%; P<.01), intermediate-density LDL (idLDL) (-14.3%; P<.05), sdLDL (-45%; P<.01), and triglycerides (-38%; P<.01) were significantly decreased, and HDL (+14.3%; P<.05) and apolipoprotein A-I (ApoA-I; +7%; P<.05) were increased; large buoyant (lb) LDL did not change (P=NS). Simvastatin therapy decreased LDL (-55.1%; P<.01), ApoB (-46%; P<.01), lbLDL (-33.3%; P<.05), idLDL (-22.7%; P<.05), sdLDL (-33.3%; P<.05), and triglycerides (-47.9%; P<.01); HDL was not changed (P=NS) after simvastatin, but ApoA-I was increased (+11.3%; P<.01). HDL increases (P<.01) and sdLDL decreases (P<.01) were significantly greater after fluvastatin compared with simvastatin therapy; LDL, triglycerides, ApoB, and idLDL changes were similar after both therapies (P=NS), and lbLDL decreases were greater with simvastatin therapy (P<.05). With both treatments, classic mean LDL and ApoB target levels were achieved in most patients. We conclude that the lipid triad can be controlled with fluvastatin XL 80 mg in patients with type 2 diabetes.

Aged↗

Biliary atresia: making the diagnosis by the gallbladder ghost triad.

OBJECTIVE: To describe the gallbladder ghost triad and evaluate its usefulness in the sonographic diagnosis of extrahepatic biliary atresia (BA). METHODS: From October 1997 to February 2002, 217 fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically. We defined the gallbladder ghost triad as gallbladder length <1.9 cm, lack of smooth/complete echogenic mucosal lining with an indistinct wall and irregular/lobular contour, and used it as a criteria for BA. Gallbladder wall thickness, triangular cord, diffuse periportal echogenicity and hepatic artery calibre were also recorded. Diagnosis of BA was confirmed surgically and histologically. RESULTS: Thirty of 31 babies with BA demonstrated the gallbladder ghost triad. No false-positives were recorded. The 31st BA baby showed a normal gallbladder at 6 weeks, but developed the ghost triad at 8 weeks. Gallbladder wall thickening was seen in 46/186 non-BA babies, but not in BA. Triangular cord was observed in 24/31 babies. Twenty-two of 186 non-BA babies and 5/31 BA babies showed diffuse periportal echogenicity. The hepatic artery appeared more prominent in BA. All 31 babies diagnosed sonographically as BA had surgery. Three non-BA babies had "negative" laparotomies showing hypoplastic bile ducts. CONCLUSIONS: The gallbladder ghost triad is a very accurate sign of BA. Indeterminate cases require close follow-up.

Bile Ducts, Extrahepatic↗

A catalytic triad is required by the non-heme haloperoxidases to perform halogenation.

The bacterial non-heme haloperoxidases are highly related to an esterase from Pseudomonas fluorescens, at structural and functional levels. Both types of enzymes displayed brominating activity and esterase activity. The presence of the serine-hydrolase motif Gly-X-Ser-X-Gly, in the esterase as well as in all aligned haloperoxidase sequences, strongly suggested that they belong to the serine-hydrolase family. Sequence alignment with several serine-hydrolases and secondary structure superimposition revealed the striking conservation of structural features characterising the alpha/beta-hydrolase fold structure in all haloperoxidases. These structural predictions allowed us to identify a potential catalytic triad in haloperoxidases, perfectly matching the triad of all aligned serine-hydrolases. The structurally equivalent triad in the chloroperoxidase CPO-P comprised the amino acids Serine 97, Aspartic acid 229 and Histidine 258. The involvement of this catalytic triad in halogenation was further assessed by inhibition studies and site-directed mutagenesis. Inactivation of CPO-P by PMSF and DEPC strongly suggested that the serine residue from the serine-hydrolase motif and an histidine residue are essential for halogenation, similar to that demonstrated for typical serine-hydrolases. By site-directed mutagenesis of CPO-P, Ser-97 was exchanged against alanine or cysteine, Asp-229 against alanine and His-258 against glutamine. Western blot analysis indicated that each mutant gene was efficiently expressed. Whereas the mutant S97C conserved a very low residual activity, each other mutant S97A, D229A or H258Q was totally inactive. This study gives the direct demonstration of the requirement of a catalytic triad in the halogenation mechanism.

Amino Acid Sequence↗

Carney triad: case report and molecular analysis of gastric tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract. Most of them are thought to be sporadic, but some arise in the settings of neurofibromatosis type I (NF-1) and the Carney triad. The Carney triad is a syndrome of unknown etiology, occurring predominantly in young females, comprising gastrointestinal stromal tumors, pulmonary chondromas, and extra-adrenal paragangliomas. GISTs of the Carney triad involve predominantly the body and the antrum of the stomach, are generally multifocal, and have a better prognosis than sporadic GISTs. We describe the clinical and pathological features of a case of Carney triad that featured multiple gastric GISTs, mediastinal paraganglioma, and esophageal leiomyoma. Ten years after gastric resection, the patient developed liver and peritoneal metastasis and was treated with Imatinib mesylate for 6 months with no change in the lesions. The molecular analysis of the GIST, the first reported in a gastric tumor from the triad, showed a wild-type KIT and PDGFRA genes.

Adult↗

Ca2+ release by inositol-trisphosphorothioate in isolated triads of rabbit skeletal muscle.

The effectiveness of the nonmetabolizable second messenger analogue DL-myo-inositol 1,4,5-trisphosphorothioate (IPS3) described by Cooke, A. M., R. Gigg, and B. V. L. Potter, (1987b. Jour. Chem. Soc. Chem. Commun. 1525-1526.) was examined in triads purified from rabbit skeletal muscle. A Ca2+ electrode uptake-release assay was used to determine the size and sensitivity of the IPS3-releasable pool of Ca2+ in isolated triads. Uptake was initiated by 1 mM MgATP, pCa 5.8, pH 7.5 Release was initiated when the free Ca2+ had lowered to pCa approximately 7. We found that 5-25 microM myo-inositol 1,4,5-trisphosphate (IP3), and separately IPS3, consistently released 5-20% of the Ca2+ pool actively loaded into triads. Single channel recording was used to determine if ryanodine receptor Ca2+ release channels were affected by IPS3 at the same myoplasmic Ca2+ and IPS3 concentrations. Open probability of ryanodine receptor Ca2+ release channels was monitored in triads fused to bilayers over long periods (200 s) in the absence and following addition of 30 microM IPS3 to the same channel. At myoplasmic pCa approximately 7, IPS3 had no effect in the absence of MgATP (Po = 0.0094 +/- 0.001 in control and Po = 0.01 +/- 0.006 after IPS3) and slightly increased activity in the presence of 1 mM MgATP (Po = 0.024 +/- 0.03 in control and Po = 0.05 +/- 0.03 after IPS3). Equally small effects were observed at higher myoplasmic Ca2+. The onset of channel activation by IPS3 or IP3 was slow, on the time scale 20-60 s. We suggest that in isolated triads of rabbit skeletal muscle, IP3-induced release of stored Ca2+ is probably not mediated by the opening of Ca2+ release channels.

Animals↗

Conservation of cys-cys trp structural triads and their geometry in the protein domains of immunoglobulin superfamily members.

In almost all members of the immunoglobulin superfamily (IgSF) for which an experimental structure has been determined, a triad (C-CW) consisting of two cysteine residues that form a disulfide bond and a neighboring tryptophan can be found in the core of the protein fold. We analyzed the geometry of these C-CW triads among a database of 60 Fab crystal structures and found it to be remarkably conserved. We identified C-CW triads of a similar configuration in other members of the IgSF such as T cell receptor (TCR), major histocompatibility complex antigens (MHC), cell surface antigens CD4 and CD8, and cell-adhesion molecules. We used this C-CW pattern to search a database of non-IgSF proteins, and identified several proteins that contain a disulfide bridge associated with a tryptophan in a similar configuration. Examination of the distances and orientations between triads found in adjacent domains in Fab fragments and TCR also reveal a high degree of conservation, which reflects the invariance of the inter-chain domain packing. This high degree of conservation of the geometry of the C-CW triad in IgSF structures suggests that the Trp may contribute significantly to the stability of the disulfide bond. Knowledge of these geometric parameters may prove useful in the construction and validation of theoretical models of Ig, TCR, and other IgSF members.

Animals↗

Synthesis, structure, characterization, and photophysical studies of a new platinum terpyridyl-based triad with covalently linked donor and acceptor groups.

A new terpyridyl-containing Pt triad [Pt(pytpy)(p-CC-C6H4-NH-CO-C6H2(OMe)3)](PF6)2 (4), where pytpy = 4'-(4-pyridin-1-ylmethylphenyl)-[2,2';6',2' ']terpyridine and p-CC-C6H4-NH-CO-C6H2(OMe)3 = N-(4-ethynylphenyl)-3,4,5-trimethoxybenzamide, has been synthesized and structurally characterized. The related donor-chromophore dyad [Pt(ttpy)(p-CC-C6H4-NH-CO-C6H2(OMe)3)]PF6 2, where ttpy = 4'-p-tolyl-[2,2';6',2' ']terpyridine, and the chromophore-acceptor dyad [Pt(pytpy)(CCC6H5)](PF6)2 (3), where CCC6H5 = ethynylbenzene, have also been studied. The multistep syntheses culminate with a CuI-catalyzed coupling reaction of the respective acetylene with either [Pt(ttpy)Cl]PF6 or [Pt(pytpy)Cl](PF6)2. X-ray and spectroscopic studies support assignment of a distorted square planar environment around the Pt(II) ion with three of its coordination sites occupied by the terpyridyl N-donors and the fourth coordination site occupied by the acetylenic carbon. Although the parent compound [Pt(ttpy)(CCC6H5)]PF6 (1) is brightly luminescent in fluid solution at 298 K, dyad 2 as well as triad 4 exhibit complete quenching of the emission. The chromophore-acceptor (C-A) dyad 3 displays weak solution luminescence at room temperature with a phi(rel)(em) of 0.011 (using Ru(bpy)3(2+) as a standard with phi(rel)(em) = 0.062). Electrochemically, the donor-chromophore (D-C) dyad and the donor-chromophore-acceptor (D-C-A) triad exhibit both metal-based and donor ligand-based oxidations, whereas the triad and the C-A dyad show the expected pyridinium- and terpyridine-based reductions. Transient absorption studies of the dyad and triad systems indicate that although the trimethoxybenzene group acts as a reductive donor, in the present system, the pyridinium group fails to act as an acceptor.

Carbon↗

Photonic switching of photoinduced electron transfer in a dihydropyrene-porphyrin-fullerene molecular triad.

Photonic control of photoinduced electron transfer has been demonstrated in a dimethyldihydropyrene (DHP) porphyrin (P) fullerene (C(60)) molecular triad. In the DHP-P-C(60) form of the triad, excitation of the porphyrin moiety is followed by photoinduced electron transfer to give a DHP-P(*)(+)-C(60)(*)(-) charge-separated state, which evolves by a charge shift reaction to DHP(*)(+)-P-C(60)(*)(-). This final state has a lifetime of 2 micros and is formed in an overall yield of 94%. Visible (>or=300 nm) irradiation of the triad leads to photoisomerization of the DHP moiety to the cyclophanediene (CPD). Excitation of the porphyrin moiety of CPD-P-C(60) produces a short-lived (<10 ns) CPD-P(*)(+)-C(60)(*)(-) state, but charge shift to the CPD moiety does not occur, due to the relatively high oxidation potential of the CPD group. Long-lived charge separation is not observed. Irradiation of CPD-P-C(60) with UV (254 nm) light converts the triad back to the DHP form. Thermal interconversion of the DHP and CPD forms is very slow, photochemical cycling is facile, and in the absence of oxygen, many cycles may be performed without substantial degradation. Thus, light is used to switch long-lived photoinduced charge separation on or off. The principles demonstrated by the triad may be useful for the design of molecule-based optoelectronic systems.

Journal Article↗

Children's interactions in triads: behavioral profiles and effects of gender and patterns of friendships among members.

In all, 56 triads of same-sex 3rd-, 4th-, and 5th-grade children were observed during an intimate discussion, a cooperative puzzle task, a competitive game, and free play. Observers coded triadic interaction using a Q sort and individual process ratings. Of particular interest was how gender and the pattern of friendship ties among group members related to children's behavior. Triads of girls were more intimate, exchanged more information, and were less aggressive than were triads of boys. Analyses of within-gender variability revealed 2 prototypical types of triads among boys but only 1 among girls. Girls and boys expressed similar attitudes toward triadic interaction in postsession interviews. However, girls', but not boys', attitudes were closely linked to the quality of interactions during the session. For both sexes, interaction was not strongly influenced by the initial configuration of friendship ties among triad members.

Age Factors↗

Perceived pitch class of isolated musical triads.

A paired-comparisons task was used to determine which note of a pure-tone triad sounded most similar to the triad. Musically inexperienced Ss showed no systematic preference, experienced Ss consistently preferred the highest note in the triad, and professional musicians split equally between preferring the highest note and the root note. Preference for the root note shifted to preference for the highest note as the triad type became increasingly inharmonic, suggesting that the former depended on inference of a missing fundamental. When Ss were asked to vocally reproduce the pitch they heard when listening to a triad, similar results were obtained, except that a root-note preference was not detectable in Ss with less musical experience. Preference for the root note was also facilitated by use of octave-replicated tones, and this increase was shown to be due to obscuring of pitch-height cues, rather than harmonic complexity.

Adult↗

Validation of a food-frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: the method of triads model.

BACKGROUND: Reliability or validity studies are important for the evaluation of measurement error in dietary assessment methods. An approach to validation known as the method of triads uses triangulation techniques to calculate the validity coefficient of a food-frequency questionnaire (FFQ). OBJECTIVE: To assess the validity of an FFQ estimates of carotenoid and vitamin E intake against serum biomarker measurements and weighed food records (WFRs), by applying the method of triads. DESIGN: The study population was a sub-sample of adult participants in a randomised controlled trial of beta-carotene and sunscreen in the prevention of skin cancer. Dietary intake was assessed by a self-administered FFQ and a WFR. Nonfasting blood samples were collected and plasma analysed for five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene) and vitamin E. Correlation coefficients were calculated between each of the dietary methods and the validity coefficient was calculated using the method of triads. The 95% confidence intervals for the validity coefficients were estimated using bootstrap sampling. RESULTS: The validity coefficients of the FFQ were highest for alpha-carotene (0.85) and lycopene (0.62), followed by beta-carotene (0.55) and total carotenoids (0.55), while the lowest validity coefficient was for lutein (0.19). The method of triads could not be used for beta-cryptoxanthin and vitamin E, as one of the three underlying correlations was negative. CONCLUSIONS: Results were similar to other studies of validity using biomarkers and the method of triads. For many dietary factors, the upper limit of the validity coefficients was less than 0.5 and therefore only strong relationships between dietary exposure and disease will be detected.

Adult↗

Abnormal formation of sarcoplasmic reticulum networks and triads during early development of skeletal muscle cells in mitsugumin29-deficient mice.

Recently, we detected a novel membrane protein, mitsugumin29 (MG29), in the triads in rabbit skeletal muscle cells and suggested important roles for this membrane protein in the formation of the sarcoplasmic reticulum (SR) networks and triads in muscle cells. In the present study, we examined the development of skeletal muscle cells in MG29-deficient mice to try to determine the roles played by MG29 in the formation of the SR networks and triads. Ultrastructural observations revealed some morphological abnormalities in these mice, such as incomplete formation of the SR networks, an irregular running of the transverse tubule and a partial defect in the triads at the A-I junctional region. These ultrastructural abnormalities occurred during early myogenesis and were preserved until the adult stage. The possible roles for MG29 in the formation of SR networks and triads in skeletal muscle cells are discussed in the light of these observations.

Animals↗